miR-126 regulates angiogenesis in myocardial ischemia by targeting HIF-1α

Exp Cell Res. 2021 Dec 15;409(2):112925. doi: 10.1016/j.yexcr.2021.112925. Epub 2021 Nov 14.

Abstract

Promoting angiogenesis by targeting various angiogenic regulators has emerged as a new treatment strategy for myocardial ischemia (MI). MicroRNA-126 (miR-126) has been identified as the main regulator of compensatory angiogenesis; however, its role in MI is unclear. A rat MI model and an EA. hy926 endothelial cell hypoxia model were constructed and it was found that miR-126 was highly expressed in both models. The knockdown of HIF-1α expression in EA. hy926 cells in turn downregulated VEGF and CD34 expression and consequently inhibited angiogenesis. MiR-126 inhibitor inhibited EA. hy926 cell migration and tube formation as well as downregulated VEGF and CD34 expression, and these were reversed by transfection of miR-126 mimics. Rescue tests using miR-126 and HIF-1α demonstrated that miR-126-mediated regulation of angiogenesis was dependent on HIF-1α. In summary, miR-126 regulates the occurrence and progression of angiogenesis during MI via HIF-1α and may be a potential new therapeutic target.

Keywords: Angiogenesis; HIF-1α; Myocardial ischemia; miR-126.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / chemistry*
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • Cell Hypoxia
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Myocardial Ischemia / genetics
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / pathology*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antigens, CD34
  • HIF1A protein, human
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN126 microRNA, human
  • MIRN126 microRNA, rat
  • MicroRNAs
  • Vascular Endothelial Growth Factor A